Google Genomics implements the GA4GH variants API and this R package can retrieve data from that implementation. For more detail, see https://cloud.google.com/genomics/v1beta2/reference/variants
library(GoogleGenomics)
# This vignette is authenticated on package load from the env variable GOOGLE_API_KEY.
# When running interactively, call the authenticate method.
# ?authenticateBy default, this function retrieves variants for a small genomic region from the 1,000 Genomes phase 1 variants.
variants <- getVariants()## Fetching variants page.## Variants are now available.length(variants)## [1] 4We can see that 4 individual variants were returned and that the JSON response was deserialized into an R list object:
class(variants)## [1] "list"mode(variants)## [1] "list"The top level field names are:
names(variants[[1]])## [1] "variantSetId" "id" "names" "created"
## [5] "referenceName" "start" "end" "referenceBases"
## [9] "alternateBases" "quality" "filter" "info"
## [13] "calls"The variant contains nested calls:
length(variants[[1]]$calls)## [1] 1092With top level call field names:
names(variants[[1]]$calls[[1]])## [1] "callSetId" "callSetName" "genotype"
## [4] "phaseset" "genotypeLikelihood" "info"And examining a call for a particular variant:
variants[[1]]$referenceName## [1] "22"variants[[1]]$start## [1] "16051452"variants[[1]]$alternateBases## [[1]]
## [1] "C"variants[[1]]$calls[[1]]## $callSetId
## [1] "10473108253681171589-0"
##
## $callSetName
## [1] "HG00261"
##
## $genotype
## $genotype[[1]]
## [1] 0
##
## $genotype[[2]]
## [1] 0
##
##
## $phaseset
## [1] "*"
##
## $genotypeLikelihood
## $genotypeLikelihood[[1]]
## [1] -0.1
##
## $genotypeLikelihood[[2]]
## [1] -0.67
##
## $genotypeLikelihood[[3]]
## [1] -3.3
##
##
## $info
## $info$DS
## $info$DS[[1]]
## [1] "0.000"This is good, but this data becomes much more useful when it is converted to Bioconductor data types. For example, we can convert variants in this list representation to VRanges from VariantAnnotation:
variantsToVRanges(variants)## VRanges object with 4 ranges and 2 metadata columns:
## seqnames ranges strand ref alt
## <Rle> <IRanges> <Rle> <character> <characterOrRle>
## rs143503259 chr22 16051453 * A C
## rs192339082 chr22 16051477 * C A
## rs79725552 chr22 16051480 * T C
## rs141578542 chr22 16051497 * A G
## totalDepth refDepth altDepth sampleNames
## <integerOrRle> <integerOrRle> <integerOrRle> <factorOrRle>
## rs143503259 <NA> <NA> <NA> <NA>
## rs192339082 <NA> <NA> <NA> <NA>
## rs79725552 <NA> <NA> <NA> <NA>
## rs141578542 <NA> <NA> <NA> <NA>
## softFilterMatrix | QUAL FILTER
## <matrix> | <numeric> <character>
## rs143503259 | 100 PASS
## rs192339082 | 100 PASS
## rs79725552 | 100 PASS
## rs141578542 | 100 PASS
## -------
## seqinfo: 1 sequence from an unspecified genome; no seqlengths
## hardFilters: NULLNext let’s use package VariantAnnotation to annotate some specific 1,000 Genomes Phase 1 variants.
library(VariantAnnotation)Note that the parameters start and end are expressed in 0-based coordinates per the GA4GH specification but the Bioconductor data type converters in GoogleGenomics, by default, transform the returned data to 1-based coordinates.
granges <- getVariants(variantSetId="10473108253681171589",
chromosome="22",
start=50300077,
end=50303000,
converter=variantsToGRanges)## Fetching variants page.## Continuing variant query with the nextPageToken: CIWK_hcQ_Nr-8ZGlk78i## Fetching variants page.## Continuing variant query with the nextPageToken: CIaM_hcQvM_un46SmcJ0## Fetching variants page.## Continuing variant query with the nextPageToken: CJGN_hcQiYna3cSwse_RAQ## Fetching variants page.## Continuing variant query with the nextPageToken: CMKQ_hcQr9OUpKu4n_xz## Fetching variants page.## Continuing variant query with the nextPageToken: CMKS_hcQn-nIneaph7WJAQ## Fetching variants page.## Continuing variant query with the nextPageToken: CKOU_hcQ2eCCwsmBysdd## Fetching variants page.## Continuing variant query with the nextPageToken: CLWV_hcQmo-n-tX08uPyAQ## Fetching variants page.## Continuing variant query with the nextPageToken: CMqX_hcQ__3H4KKV9tUR## Fetching variants page.## Continuing variant query with the nextPageToken: CKuZ_hcQ9pHXwa742bKgAQ## Fetching variants page.## Continuing variant query with the nextPageToken: CLqa_hcQ-6zjo_Dc86gy## Fetching variants page.## Continuing variant query with the nextPageToken: CLSb_hcQ3vrDo5XJwsB_## Fetching variants page.## Continuing variant query with the nextPageToken: CKOd_hcQ6IPgk-PVjskK## Fetching variants page.## Continuing variant query with the nextPageToken: CPGe_hcQ-8Saw6Ojg8yXAQ## Fetching variants page.## Continuing variant query with the nextPageToken: CPGf_hcQuKDdodiCvLUm## Fetching variants page.## Variants are now available.Now locate the protein coding variants in each:
library(TxDb.Hsapiens.UCSC.hg19.knownGene)txdb <- TxDb.Hsapiens.UCSC.hg19.knownGene
granges_locations <- locateVariants(granges, txdb, CodingVariants())## Warning in valid.GenomicRanges.seqinfo(x, suggest.trim = TRUE): GRanges object contains 1 out-of-bound range located on sequence
## 75253. Note that ranges located on a sequence whose length is
## unknown (NA) or on a circular sequence are not considered
## out-of-bound (use seqlengths() and isCircular() to get the lengths
## and circularity flags of the underlying sequences). You can use
## trim() to trim these ranges. See ?`trim,GenomicRanges-method` for
## more information.## 'select()' returned many:1 mapping between keys and columnsgranges_locations## GRanges object with 7 ranges and 9 metadata columns:
## seqnames ranges strand | LOCATION LOCSTART LOCEND QUERYID
## <Rle> <IRanges> <Rle> | <factor> <integer> <integer> <integer>
## [1] chr22 50301422 - | coding 939 939 24
## [2] chr22 50301476 - | coding 885 885 25
## [3] chr22 50301488 - | coding 873 873 26
## [4] chr22 50301494 - | coding 867 867 27
## [5] chr22 50301584 - | coding 777 777 28
## [6] chr22 50302962 - | coding 698 698 57
## [7] chr22 50302995 - | coding 665 665 58
## TXID CDSID GENEID PRECEDEID FOLLOWID
## <character> <IntegerList> <character> <CharacterList> <CharacterList>
## [1] 75253 218562 79087 <NA> <NA>
## [2] 75253 218562 79087 <NA> <NA>
## [3] 75253 218562 79087 <NA> <NA>
## [4] 75253 218562 79087 <NA> <NA>
## [5] 75253 218562 79087 <NA> <NA>
## [6] 75253 218563 79087 <NA> <NA>
## [7] 75253 218563 79087 <NA> <NA>
## -------
## seqinfo: 1 sequence from an unspecified genome; no seqlengthsAnd predict the effect of the protein coding variants:
library(BSgenome.Hsapiens.UCSC.hg19)granges_coding <- predictCoding(rep(granges, elementNROWS(granges$ALT)),
txdb,
seqSource=Hsapiens,
varAllele=unlist(granges$ALT, use.names=FALSE))## Warning in valid.GenomicRanges.seqinfo(x, suggest.trim = TRUE): GRanges object contains 1 out-of-bound range located on sequence
## 75253. Note that ranges located on a sequence whose length is
## unknown (NA) or on a circular sequence are not considered
## out-of-bound (use seqlengths() and isCircular() to get the lengths
## and circularity flags of the underlying sequences). You can use
## trim() to trim these ranges. See ?`trim,GenomicRanges-method` for
## more information.granges_coding## GRanges object with 7 ranges and 16 metadata columns:
## seqnames ranges strand | REF ALT
## <Rle> <IRanges> <Rle> | <DNAStringSet> <DNAStringSetList>
## rs114335781 chr22 50301422 - | G A
## rs8135963 chr22 50301476 - | T C
## rs200080075 chr22 50301488 - | C T
## rs147801200 chr22 50301494 - | G A
## rs138060012 chr22 50301584 - | C T
## rs114264124 chr22 50302962 - | C T
## rs149209714 chr22 50302995 - | C G
## QUAL FILTER varAllele CDSLOC PROTEINLOC
## <numeric> <character> <DNAStringSet> <IRanges> <IntegerList>
## rs114335781 100 PASS T 939 313
## rs8135963 100 PASS G 885 295
## rs200080075 100 PASS A 873 291
## rs147801200 100 PASS T 867 289
## rs138060012 100 PASS A 777 259
## rs114264124 100 PASS A 698 233
## rs149209714 100 PASS C 665 222
## QUERYID TXID CDSID GENEID CONSEQUENCE
## <integer> <character> <IntegerList> <character> <factor>
## rs114335781 24 75253 218562 79087 synonymous
## rs8135963 25 75253 218562 79087 synonymous
## rs200080075 26 75253 218562 79087 synonymous
## rs147801200 27 75253 218562 79087 synonymous
## rs138060012 28 75253 218562 79087 synonymous
## rs114264124 57 75253 218563 79087 nonsynonymous
## rs149209714 58 75253 218563 79087 nonsynonymous
## REFCODON VARCODON REFAA VARAA
## <DNAStringSet> <DNAStringSet> <AAStringSet> <AAStringSet>
## rs114335781 ATC ATT I I
## rs8135963 GCA GCG A A
## rs200080075 CCG CCA P P
## rs147801200 CAC CAT H H
## rs138060012 CCG CCA P P
## rs114264124 CGG CAG R Q
## rs149209714 GGA GCA G A
## -------
## seqinfo: 1 sequence from an unspecified genome; no seqlengthsFinally, add gene information:
library(org.Hs.eg.db)annots <- select(org.Hs.eg.db,
keys=granges_coding$GENEID,
keytype="ENTREZID",
columns=c("SYMBOL", "GENENAME","ENSEMBL"))## 'select()' returned many:1 mapping between keys and columnscbind(elementMetadata(granges_coding), annots)## DataFrame with 7 rows and 20 columns
## REF ALT QUAL FILTER varAllele
## <DNAStringSet> <DNAStringSetList> <numeric> <character> <DNAStringSet>
## 1 G A 100 PASS T
## 2 T C 100 PASS G
## 3 C T 100 PASS A
## 4 G A 100 PASS T
## 5 C T 100 PASS A
## 6 C T 100 PASS A
## 7 C G 100 PASS C
## CDSLOC PROTEINLOC QUERYID TXID CDSID GENEID
## <IRanges> <IntegerList> <integer> <character> <IntegerList> <character>
## 1 939 313 24 75253 218562 79087
## 2 885 295 25 75253 218562 79087
## 3 873 291 26 75253 218562 79087
## 4 867 289 27 75253 218562 79087
## 5 777 259 28 75253 218562 79087
## 6 698 233 57 75253 218563 79087
## 7 665 222 58 75253 218563 79087
## CONSEQUENCE REFCODON VARCODON REFAA VARAA
## <factor> <DNAStringSet> <DNAStringSet> <AAStringSet> <AAStringSet>
## 1 synonymous ATC ATT I I
## 2 synonymous GCA GCG A A
## 3 synonymous CCG CCA P P
## 4 synonymous CAC CAT H H
## 5 synonymous CCG CCA P P
## 6 nonsynonymous CGG CAG R Q
## 7 nonsynonymous GGA GCA G A
## ENTREZID SYMBOL GENENAME
## <character> <character> <character>
## 1 79087 ALG12 ALG12, alpha-1,6-mannosyltransferase
## 2 79087 ALG12 ALG12, alpha-1,6-mannosyltransferase
## 3 79087 ALG12 ALG12, alpha-1,6-mannosyltransferase
## 4 79087 ALG12 ALG12, alpha-1,6-mannosyltransferase
## 5 79087 ALG12 ALG12, alpha-1,6-mannosyltransferase
## 6 79087 ALG12 ALG12, alpha-1,6-mannosyltransferase
## 7 79087 ALG12 ALG12, alpha-1,6-mannosyltransferase
## ENSEMBL
## <character>
## 1 ENSG00000182858
## 2 ENSG00000182858
## 3 ENSG00000182858
## 4 ENSG00000182858
## 5 ENSG00000182858
## 6 ENSG00000182858
## 7 ENSG00000182858sessionInfo()## R version 3.5.0 (2018-04-23)
## Platform: x86_64-apple-darwin15.6.0 (64-bit)
## Running under: OS X El Capitan 10.11.6
##
## Matrix products: default
## BLAS: /Library/Frameworks/R.framework/Versions/3.5/Resources/lib/libRblas.0.dylib
## LAPACK: /Library/Frameworks/R.framework/Versions/3.5/Resources/lib/libRlapack.dylib
##
## locale:
## [1] C/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8
##
## attached base packages:
## [1] stats4 parallel stats graphics grDevices utils datasets
## [8] methods base
##
## other attached packages:
## [1] org.Hs.eg.db_3.6.0
## [2] BSgenome.Hsapiens.UCSC.hg19_1.4.0
## [3] BSgenome_1.48.0
## [4] rtracklayer_1.40.0
## [5] TxDb.Hsapiens.UCSC.hg19.knownGene_3.2.2
## [6] GenomicFeatures_1.32.0
## [7] AnnotationDbi_1.42.0
## [8] GoogleGenomics_2.2.0
## [9] VariantAnnotation_1.26.0
## [10] GenomicAlignments_1.16.0
## [11] Rsamtools_1.32.0
## [12] Biostrings_2.48.0
## [13] XVector_0.20.0
## [14] SummarizedExperiment_1.10.0
## [15] DelayedArray_0.6.0
## [16] BiocParallel_1.14.0
## [17] matrixStats_0.53.1
## [18] Biobase_2.40.0
## [19] GenomicRanges_1.32.0
## [20] GenomeInfoDb_1.16.0
## [21] IRanges_2.14.0
## [22] S4Vectors_0.18.0
## [23] BiocGenerics_0.26.0
## [24] knitr_1.20
## [25] BiocStyle_2.8.0
##
## loaded via a namespace (and not attached):
## [1] progress_1.1.2 xfun_0.1 lattice_0.20-35
## [4] htmltools_0.3.6 yaml_2.1.18 blob_1.1.1
## [7] XML_3.98-1.11 DBI_0.8 bit64_0.9-7
## [10] GenomeInfoDbData_1.1.0 stringr_1.3.0 zlibbioc_1.26.0
## [13] evaluate_0.10.1 memoise_1.1.0 biomaRt_2.36.0
## [16] curl_3.2 Rcpp_0.12.16 backports_1.1.2
## [19] jsonlite_1.5 bit_1.1-12 rjson_0.2.15
## [22] digest_0.6.15 stringi_1.1.7 bookdown_0.7
## [25] grid_3.5.0 rprojroot_1.3-2 tools_3.5.0
## [28] bitops_1.0-6 magrittr_1.5 RCurl_1.95-4.10
## [31] RSQLite_2.1.0 pkgconfig_2.0.1 Matrix_1.2-14
## [34] prettyunits_1.0.2 assertthat_0.2.0 rmarkdown_1.9
## [37] httr_1.3.1 R6_2.2.2 compiler_3.5.0